ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.4168A>T (p.Met1390Leu)

gnomAD frequency: 0.00001  dbSNP: rs754311975
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001302684 SCV001491902 uncertain significance Hyperkalemic periodic paralysis 2023-08-02 criteria provided, single submitter clinical testing This variant is present in population databases (rs754311975, gnomAD 0.006%). This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1390 of the SCN4A protein (p.Met1390Leu). This variant has not been reported in the literature in individuals affected with SCN4A-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SCN4A protein function. ClinVar contains an entry for this variant (Variation ID: 1005752).
Fulgent Genetics, Fulgent Genetics RCV005014370 SCV005651719 uncertain significance Potassium-aggravated myotonia; Paramyotonia congenita of Von Eulenburg; Hypokalemic periodic paralysis, type 2; Hyperkalemic periodic paralysis; Congenital myasthenic syndrome 16; Congenital myopathy 22A, classic; Congenital myopathy 22B, severe fetal 2024-05-21 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004545192 SCV004781211 uncertain significance SCN4A-related disorder 2023-11-20 no assertion criteria provided clinical testing The SCN4A c.4168A>T variant is predicted to result in the amino acid substitution p.Met1390Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0070% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-62020306-T-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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